Rabbit pulmonary monooxygenase system: catalytic differences between two purified forms of cytochrome P-450 in the metabolism of benzo(a)pyrene
The metabolism and activation of the pulmonary carcinogen, benzo(a)pyrene, have been examined in reconstituted rabbit pulmonary monooxygenase systems. Two forms of purified pulmonary cytochrome P-450, which are known to have different monomeric molecular weights, spectral properties, and substrate specificities, were compared. Metabolite profiles were obtained using high pressure liquid chromatography. Metabolites that chromatographed with the 3-hydroxy and quinone standards accounted for 95% of the total activity of cytochrome I. With cytochrome II metabolism at positions 9 and 10 accounted for 40 to 50% of the total activity; products that chromatographed with the 3-hydroxy standard were 30 to 40% of the total. Formation of the 4,5- or 7,8-dihydrodiol metabolites accounted for less than 5% of the total produced by either cytochrome. The metabolism of benzo(a)pyrene by cytochrome II was inhibited by ..cap alpha..-naphthoflavone (K/sub i/ = 8.2 +- 0.4 x 10/sup -9/ M) in a manner that did not affect the profile of the metabolites produced. Metabolism by cytochrome I was not significantly inhibited by ..cap alpha..-naphthoflavone at a concentration of 10/sup -4/ M. Cytochrome II, unlike cytochrome I, catalyzed the metabolism of benzo(a)pyrene to products that bound covalently to DNA. The involvement of the two pulmonary cytochromes in the formation of potentially carcinogenic metabolites from benzo(a)pyrene is discussed.
- Research Organization:
- National Inst. of Environmental Health Sciences, Research Triangle Park, NC
- OSTI ID:
- 5338260
- Journal Information:
- J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 254:9; ISSN JBCHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BENZOPYRENE
BIOCHEMICAL REACTION KINETICS
BODY
COMPARATIVE EVALUATIONS
CONDENSED AROMATICS
CYTOCHROMES
DNA
ENZYME ACTIVITY
ENZYME INHIBITORS
HYDROCARBONS
KINETICS
LUNGS
MAMMALS
METABOLISM
METABOLITES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PIGMENTS
RABBITS
REACTION KINETICS
RESPIRATORY SYSTEM
TOXICITY
VERTEBRATES